IPI Score Research Articles

Correlation between Immune Microenvironment and Clinicopathological Characteristics and Prognosis of Primary Large B-cell Lymphoma of Immune-Privileged Sites

ObjectivesTo explore the correlation between tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and tumor-associated angiogenesis (TAA) in the tumor microenvironment with the clinicopathological characteristics and prognosis of primary large B-cell lymphoma of immune-privileged sites (LBCL-IP).MethodsA total of 46 cases of LBCL-IP from the Department of Pathology, the Third Affiliated Hospital of Xinjiang Medical University, from January 2010 to February 2024, were collected, along with clinical and follow-up data of LBCL-IP patients. Immunohistochemistry and triple immunofluorescence were used to detect related proteins of TAMs, TILs, and TAA, and to analyze the correlation between TAMs, TILs, TAA, and the polarization of TAMs with the clinical and prognostic factors of LBCL-IP patients.ResultsThere are 30 cases (65.2%) showed high expression of CD68 proteins, 32 cases (69.6%) showed high expression of CD163 proteins, 19 cases (41.3%) showed high expression of CD4 proteins, 34 cases (73.9%) showed high expression of CD8 proteins, and 25 cases (54.3%) showed high expression of CD34 proteins. A total of 27 cases (58.7%) showed CD68+CD163+/CD68+CD86+≥1. The chi-square tests showed that high expression of CD163 proteins was positively correlated with elevated LDH and BMG values, and the count of CD68+CD163+/CD68+CD86+≥1 was positively correlated with ECOG scores ≥2, Ann Arbor staging III-IV, and increased BMG value. High expression of CD8 proteins was positively correlated with a Ki-67 proliferation index ≥70%, and high MVD values were positively correlated with Ann Arbor staging III-IV. The Kaplan-Meier estimator analysis showed that LBCL-IP patients with low expression of CD68 proteins, high expression of CD163 proteins, CD68+CD163+/CD68+CD86+≥1, low expression of CD8 proteins, high MVD values, ECOG scores ≥2, Ann Arbor staging III-IV, LDH ≥250U/L, BMG ≥2.2mg/L, and IPI scores ≥2 had shorter survival times. Multivariate Cox regression analysis showed that low expression of CD8 proteins, CD68+CD163+/CD68+CD86+≥1, LDH ≥250U/L, and ECOG scores ≥2 are independent risk factors affecting the survival of LBCL-IP patients.ConclusionM2-polarized TAMs and low infiltration of CD8+ TILs were more strongly correlated with poor clinical pathological indicators and worse prognosis, and MVD values may serve as an aiding means for the diagnosis and prognostic prediction of LBCL-IP disease.

CODOX-M/IVAC-R versus DA-EPOCH-R in double hit/triple hit lymphoma patients aged 60 years or under.

Intensified chemoimmunotherapy regimens are often used in young patients with double hit and triple hit lymphoma (DHL/THL) despite no survival benefit compared to R-CHOP. Favorable retrospective reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate this treatment. We conducted a retrospective analysis to investigate outcome differences between CODOX-M/IVAC-R and DA-EPOCH-R in DHL/THL patients aged 60 years or younger. 113 patients were identified; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). 80% (39/49) achieved complete (CR) after completing CODOX-M/IVAC-R compared to 58% (37/64) with DA-EPOCH-R. The median follow-up was 5.3 years and 3.3 years for the CODOX-M/IVAC-R and DA-EPOCH-R group respectively. CODOX-M/IVAC-R demonstrated superior EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL translocation (BCL2 vs BCL6 vs both), IPI score and receipt of ASCT (aHR=0.52, 95%CI=0.29-0.93); however there was no significant influence on OS (aHR=0.92, 95%CI=0.46-1.84). The 1, 2 and 5 years EFS in the CODOX-M/IVAC-R group was 68.3%, 64.1% and 61.5% respectively compared to 52.4%, 48.9% and 39.5% respectively in the DA-EPOCH-R group. Primary refractory disease or relapse occurred in 33% (16/49) of CODOX-M/IVAC-R and 54% (35/64) of DA-EPOCH-R recipients, and produced median OS of 10.3 months and 33.7 months, respectively, indicating poor outcomes in the CODOX-M/IVAC-R subgroup with R/R disease. More patients were able to receive subsequent salvage therapies in the DA-EPOCH-R group. No patients died of regimen toxicity and the rates of CNS relapse and therapy related hematologic neoplasms were similar in both groups.

Clinical Features and Prognosis of Patients with Diffuse Large B-Cell Lymphoma of the Breast

To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast. The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed. There were significant differences in IPI score, LDH level and β2- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was （59.1±19.8）% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05). Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and β2-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.

A machine learning approach in a monocentric cohort for predicting primary refractory disease in Diffuse Large B-cell lymphoma patients.

Primary refractory disease affects 30-40% of patients diagnosed with DLBCL and is a significant challenge in disease management due to its poor prognosis. Predicting refractory status could greatly inform treatment strategies, enabling early intervention. Various options are now available based on patient and disease characteristics. Supervised machine-learning techniques, which can predict outcomes in a medical context, appear highly suitable for this purpose. Retrospective monocentric cohort study. Adult patients with a first diagnosis of DLBCL admitted to the hematology unit from 2017 to 2022. We evaluated in our Center five supervised machine-learning (ML) models as a tool for the prediction of primary refractory DLBCL. One hundred and thirty patients with Diffuse Large B-cell lymphoma (DLBCL) were included in this study between January 2017 and December 2022. The variables used for analysis included demographic characteristics, clinical condition, disease characteristics, first-line therapy and PET-CT scan realization after 2 cycles of treatment. We compared five supervised ML models: support vector machine (SVM), Random Forest Classifier (RFC), Logistic Regression (LR), Naïve Bayes (NB) Categorical classifier and eXtreme Gradient Boost (XGboost), to predict primary refractory disease. The performance of these models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, false positive rate, sensitivity, and F1-score to identify the best model. After a median follow-up of 19.5 months, the overall survival rate was 60% in the cohort. The Overall Survival at 3 years was 58.5% (95%CI, 51-68.5) and the 3-years Progression Free Survival was 63% (95%CI, 54-71) using Kaplan-Meier method. Of the 124 patients who received a first line treatment, primary refractory disease occurred in 42 patients (33.8%) and 2 patients (1.6%) experienced relapse within 6 months. The univariate analysis on refractory disease status shows age (p = 0.009), Ann Arbor stage (p = 0.013), CMV infection (p = 0.012), comorbidity (p = 0.019), IPI score (p<0.001), first line of treatment (p<0.001), EBV infection (p = 0.008) and socio-economics status (p = 0.02) as influencing factors. The NB Categorical classifier emerged as the top-performing model, boasting a ROC-AUC of 0.81 (95% CI, 0.64-0.96), an accuracy of 83%, a F1-score of 0.82, and a low false positive rate at 10% on the validation set. The eXtreme Gradient Boost (XGboost) model and the Random Forest Classifier (RFC) followed with a ROC-AUC of 0.74 (95%CI, 0.52-0.93) and 0.67 (95%CI, 0.46-0.88) respectively, an accuracy of 78% and 72% respectively, a F1-score of 0.75 and 0.67 respectively, and a false positive rate of 10% for both. The other two models performed worse with ROC-AUC of 0.65 (95%CI, 0.40-0.87) and 0.45 (95%CI, 0.29-0.64) for SVM and LR respectively, an accuracy of 67% and 50% respectively, a f1-score of 0.64 and 0.43 respectively, and a false positive rate of 28% and 37% respectively. Machine learning algorithms, particularly the NB Categorical classifier, have the potential to improve the prediction of primary refractory disease in DLBCL patients, thereby providing a novel decision-making tool for managing this condition. To validate these results on a broader scale, multicenter studies are needed to confirm the results in larger cohorts.

Effectiveness of fractionated rituximab in preventing tumor lysis syndrome in aggressive B-cell lymphoma: Insights from real-life clinical practice.

Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy. This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Data was retrospectively collected from 94 of 186 patients. Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence. In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Treatment of refractory diffuse large B-cell lymphoma involving the central nervous system with polatuzumab vedotin-based regimen: a case report and literature review

Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting CD79b, which has been shown to be effective in treating newly diagnosed and relapsed/refractory diffuse large B cell lymphoma (DLBCL) during clinical trials. This study aims to conduct a retrospective analysis of the clinical characteristics, diagnosis, and treatment of a patient with refractory secondary central nervous system lymphoma at Beijing Hospital, alongside a review of relevant literature. This study included a 79-year-old female patient who was diagnosed with DLBCL affecting the ilium, sacrum, spinal cord, and nerve roots and had an IPI score of 5 and a high-risk score according to MSKCC. She showed a geriatric comprehensive assessment (IACA) score of 2, which was categorized under the unfit group. Her initial treatment comprised chemo-free therapy and radiotherapy, followed by progression. In the second-line treatment, a Pola-based regimen was applied, and the patient achieved a complete response, suggesting that this regimen may be a therapeutic option for patients with DLBCL involving the central nervous system.

Soluble MIC-A, IPI, and response to treatment strongly predict survival in patients with germinal center diffuse large B cell lymphoma.

To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.

Clinical Features and Prognosis of Secondary Intestinal Diffuse Large B-Cell Lymphoma

To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma (SI-DLBCL), in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology. The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted, the clinical and pathological features, diagnosis, treatment and prognosis were analyzed. Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors. Among the 138 patients with SI-DLBCL included in this study, 85 (61.59%) were male, 53 (38.41%) were female, the median age of onset was 59.5 (16-84) years, the clinical manifestations lacked specificity, the first-line treatment regimen was mainly chemotherapy (67.39%), 94 cases (68.12%) received chemotherapy alone, 40 cases (28.98%) were treated with chemotherapy combined with surgery, and 4 cases (2.90%) were treated with surgery alone. The median follow-up time was 72 (1-148) months. Among the 138 patients with SI-DLBCL, 79 (57.25%) survived, 34 (24.64%) died, 25 cases (18.12%) lost to follow-up, the PFS rates of 1-year, 3-year and 5-year were 57.97%, 49.28% and 32.61%, and the OS rates of 1-year, 3-year and 5-year were 60.14%, 54.35% and 34.06%, respectively. The results of univariate Cox regression analysis showed that age, Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients, and age, Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients. The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients. Patients with SI-DLBCL are more common in middle-aged and elderly men, and the early clinical manifestations lack specificity, and the first-line treatment regimen is mainly R-CHOP chemotherapy, and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Prognostic Value of LMR and CD163+TAM for Patients with Diffuse Large B Cell Lymphoma

To investigate the prognostic value of lymphocyte-to-monocyte ratio (LMR) and CD163+tumor-associated macrophages (TAM) in patients with diffuse large B cell lymphoma (DLBCL). Peripheral blood and lymph node tissues were collected from 63 newly diagnosed DLBCL patients. LMR was calculated by the number of lymphocytes and monocytes in peripheral blood from the result of blood routine examination. The level of CD163+TAM in lymph nodes was detected by immunohistochemistry. The cut-off values of LMR and CD163+TAM were determined by ROC curves, and the prognostic value of LMR and CD163+TAM in DLBCL patients was analyzed. The LMR level of 63 newly diagnosed DLBCL patients was 3.69±1.71, and the median value of CD163+TAM was 26/HPF. The number of CD163+TAM was negatively correlated with LMR (r =-0.58) and positively correlated with monocyte count (r =0.46). The cut-off values of LMR and CD163+TAM determined by ROC curve were 2.95 and 29/HPF, respectively, and based on this, the patients were divided into low LMR group and high LMR group, as well as low CD163+TAM group and high CD163+TAM group. The proportion of patients with clinical stage III-IV, IPI score 3-5 and bone marrow infiltration in the low LMR group were higher than those in the high LMR group (P < 0.05). The proportion of patients with clinical stage III-IV, IPI score 3-5, elevated LDH level and bone marrow infiltration in the high CD163+TAM group were higher than those in the low CD163+TAM group (P < 0.05). There was a positive correlation between LMR and OS (r =0.43) and a negative correlation between CD163+TAM and OS (r =-0.65). DLBCL patients with low LMR and high CD163+TAM had shorter OS (P < 0.05). Low LMR and high CD163+TAM can be used as biological markers for poor prognosis of DLBCL patients.

A Retrospective Study of R±DHAX Regimen versus R-CHOP Regimen First-Line Treatment of Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed. Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( P =0.005 P =0.018, P =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( P =0.738, P =1, P =0.315, P =0.305, P =0.413, P =0.177, P =0.711, P =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CR［(27.8%（5/18） vs 50.0%（9/18）; P >0.05］ and PR ［44.4%（8/18） vs 50.0%（9/18）; P >0.05］ of R±DHAX group and R-CHOP group, there was statistically significant difference in ORR［72.2%（13/18） vs 100.0%（18/18）; P =0.045］ between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( P =0.001, P =0.002). The median survival time in the R±DHAX group was 11 months(95%CI :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups (P < 0.001). For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.

Comparison of the Prognostic Value of C-Reactive Protein to Albumin Ratio and Glasgow Prognostic Score in Patients with Diffuse Large B-Cell Lymphoma

To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes. ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 (P =0.002) and 0.695 (P =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years (P =0.025), ECOG score ≥2 (P =0.004), Lugano stage III-IV (P < 0.001), non-germinal center B-cell-like (non-GCB) subtype (P =0.035), elevated lactate dehydrogenase (LDH) ( P < 0.001), extranodal involved site >1 (P =0.004) and IPI score >2 (P < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% vs 80.0%, P =0.035; CRR: 63.6% vs 32.5%, P =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached vs 67 months, P =0.0026; median OS: not reached vs 67 months, P =0.002), while there was no statistical difference in PFS (P =0.11) and OS (P =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS. CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.

Prognostic Factors Affecting Recurrence in Peripheral T-Cell Lymphoma Patients with Different HDAC Levels

To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma (PTCL) patients with different levels of histone deacetylase (HDAC) based on latent class analysis. 112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group. The clinical data of the two groups of patients were compared. Multivariate logistic regression was used to analyze the risk factors for recurrence. Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group. There were 87 patients (77.68%) in recurrence group and 25 patients (22.32%) in non-recurrence group. The result of multivariate logistic regression showed that ECOG score ≥2, Ann Arbor stage III-IV, IPI score >2, bone marrow involvement, elevated serum β2-microglobulin (β2-MG), short-term efficacy not reaching complete remission (CR) or partial remission (PR), and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL (P <0.05). The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels (P <0.05). The results of cluster analysis showed that the risk of recurrence was obviously clustered, and the patients could be divided into high recurrence risk group (HDAC＞5 points) and low recurrence risk group (HDAC≤5 points). The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group, compared with the low recurrence risk group (P <0.05). There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.

Clinical Features and Prognosis of Patients with CD5+ Diffuse Large B-Cell Lymphoma

To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

Phase 3 trial evaluating efficacy and safety of odronextamab plus CHOP vs rituximab plus CHOP in previously untreated diffuse large B-cell lymphoma (DLBCL; OLYMPIA-3).

TPS7086 Background: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) remains a standard of care first-line (1L) treatment for patients (pts) with DLBCL. However, poor outcomes persist for certain DLBCL pt subgroups, including those with high-risk features: activated B-cell-like (ABC) cell of origin (5-yr progression-free survival [PFS]/overall survival [OS] 48%/56%), MYC and BCL2 rearrangements (median OS 15 months), or International Prognostic Index [IPI] score 4–5 (5-yr PFS/OS 46%/54%). Improving outcomes through effective 1L treatment continues to be important, highlighted by the dismal prognosis in pts who are primary refractory (2-yr OS 24%) or who relapse early after 1L treatment (4-yr OS 30%). Odronextamab, a CD20×CD3 bispecific antibody, showed encouraging efficacy (objective response rate 52%; complete response [CR] rate 31%; 47% maintained CR at 2 years) and generally manageable safety as a monotherapy in pts with heavily pretreated relapsed/refractory DLBCL, including in pts who were anti-CD20 antibody refractory (Ph 2 ELM-2 study; Ayyappan, et al. ASH 2023). These data provide the rationale to evaluate the efficacy and safety of odronextamab plus CHOP (O-CHOP) vs R-CHOP in pts with previously untreated DLBCL. Methods: OLYMPIA-3 (NCT06091865) is a Ph 3, randomized, open-label, multicenter study of O-CHOP vs R-CHOP in pts with previously untreated DLBCL and intermediate- or high-risk features. The study consists of Part 1A (dose escalation), Part 1B (dose optimization), and Part 2 (randomized controlled). Part 1A will assess the safety of O-CHOP. In Part 1B, pts will be randomized 1:1 to one of two O-CHOP regimens, selected based on Part 1A results. In Part 2, pts will be randomized 1:1 to O-CHOP or R-CHOP, with odronextamab dosing dependent on Part 1 results, and R-CHOP given per standard practice. Intravenous odronextamab will be administered weekly from Cycle (C) 1 Day (D) 8 until C5D8, with step-up dosing during C1 and C2, then every 2 weeks until the end of C6. CHOP will be administered in six 21-day cycles, starting on C1D1. Key inclusion criteria: aged ≥18 years; untreated CD20+ DLBCL; ECOG PS ≤2; and IPI score ≥2. Pts with central nervous system lymphoma, Grade ≥3 peripheral neuropathy, or an active infection are excluded. The primary endpoints are the incidence of dose-limiting toxicities, and incidence and severity of treatment-emergent adverse events (Part 1), and PFS by independent central review (Part 2). Part 2 key secondary endpoints are event-free survival and CR rate (both by independent central review), as well as OS. Other secondary endpoints are minimal residual disease (by ctDNA) and patient-reported outcomes (EORTC QLQ-C30, FACT-LymS, PGIS, PGIC, and EQ-5D-5L). The trial is currently recruiting and is expected to enroll up to 64 pts in Part 1 and ~840 pts in Part 2 at ~200 global sites. Clinical trial information: NCT06091865 .

Factors associated with manufacturing failure of commercial CD19 CAR-T cell products for large b cell lymphoma (LBCL).

7044 Background: As CD19 chimeric antigen receptor T-cell (CAR-T) therapy has shown curative potential in patients (pts) with relapsed/refractory (R/R) LBCL, indications for treatment are expanding. The reported manufacturing failure rate was 1-13% in clinical trials, but there is poor understanding of out-of-specification (OOS) products and CAR-T products on 2nd apheresis. This study aims to characterize factors associated with successful manufacturing. Methods: This study includes pts with R/R LBCL who underwent apheresis for CAR-T product between 12/2017 and 2/2023. Baseline variables were obtained at time of apheresis. OOS product is defined as not meeting eligibility for a commercial product but suitable for infusion on expanded access protocol. 2nd apheresis was performed due to initial manufacture failure. Progression-free survival (PFS) is the time from CAR-T conditioning to disease progression or death, whichever occurs first. Overall survival (OS) is defined as time from conditioning to death or last follow-up. A chi-square test or Fisher’s exact test was used for comparison of 2 categorical variables. Results: 319 pts underwent apheresis; 261(78%) were axicabtagene ciloleucel, 26(8%) were tisagenlecleucel and 47(14%) were lisocabtagene maraleucel 284(85%); products were in-specification (in-spec) on 1st apheresis, 8(2%) in-spec on 2nd apheresis, 27(8%) OOS, and 15(4%) manufacturing failures. Comparison of variables are in the table. OOS rates were 10/250(4%) for axicabtagene, 4/23(17.4%) for tisagenlecleucel and 13/46(28.3%) for lisocabtagene. Reason for OOS product were low viability:14, high interferon:4, internal manufacturing issue:2, CD4 lineage purity:2, high transduction:1, low transduction:2, and low vector copies:2. No association was found with clinical factors and OOS. Factors associated with OOS were advanced stage (P=0.012), IPI score &gt;3 (p=0.001), extranodal involvement (P=0.012) and older age (p= 0.002). In-spec product on 1st apheresis had greater OS (p= 0.011) and PFS (p=0.043) than 2nd apheresis. Conclusions: Factors predictive of OOS product include older age, advanced disease, extranodal involvement and high IPI. Pts requiring 2nd apheresis had worse survival. Lisocabtagene had higher likelihood for OOS product. Outcomes for OOS products are not well described. Failure to manufacture an eligible product is a barrier for LBCL pts to receive CAR-T therapy. [Table: see text]

A retrospective analysis of the clinicopathological features and prognostic value of MAPK12 protein expression in diffuse large B-cell lymphoma.

Mitogen-activated protein kinase 12 (MAPK12), also known as p38γ, is a member of the p38 MAPK family and plays a crucial role in tumor occurrence and invasion. However, there is still uncertainty regarding MAPK12 involvement in diffuse large B-cell lymphoma (DLBCL). Our study investigated the expression of MAPK12 mRNA in various types of cancer using bioinformatic analysis. Furthermore, we performed immunohistochemistry (IHC) to detect the expression of MAPK12 in patients with DLBCL and compared clinical indicators and survival rates. We found that the high expression rate of MAPK12 was 43.1% in DLBCL patients. Several clinical indicators, including IPI scores, Hans classifications, LDH levels, and Ki-67 expression were closely associated with MAPK12 expression. Survival analysis revealed that higher expression of MAPK12 was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients. In addition, both univariate and multivariate analyses revealed IPI score, MAPK12 expression, and rituximab use as the independent OS risk factors (P < 0.05). To explore the functional role of MAPK12 in DLBCL, weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to confirm the involvement of MAPK12 in the regulation of type II interferon production, positive regulation of lymphocyte proliferation, and other related biological processes. DLBCL patients have poor prognoses when MAPK12 levels are high, which is expected to be a therapeutic target and prognostic factor.

Consolidation therapy with autologous stem cell transplantation after remission of induction chemotherapy prolongs the survival of patients with peripheral T-cell lymphoma.

There was little evidence of autologous stem cell transplantation (ASCT) as consolidation therapy after remission of induction for patients with Peripheral T-cell lymphoma (PTCL). In this study, we conducted a comparative analysis of real-world survival outcomes between consolidation therapy and observation in patients with PTCL. A total of 92 patients with peripheral T-cell lymphoma (PTCL) who were admitted to the Department of Hematology, Huadong Hospital Affiliated with Fudan University from January 2013 to April 2019 were divided into two groups based on whether they were treated with high-dose therapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT): ASCT as consolidation therapy (n=30) and observation (n=62). Clinical characteristics, treatment patterns, and survival outcomes were analyzed between the two groups. Univariate and Cox multivariate regression analyses were also performed to detect prognostic factors of survival. With a median follow-up time of 41 months, the median overall survival (OS) of peripheral T-cell lymphoma patients treated with ASCT was not reached; the median progression-free survival (PFS) was 77.0 months, which was much higher than that of patients without ASCT (p<0.003 for OS, p=0.015 for PFS). Subgroup analysis found that patients with high risks benefited more from ASCT. Combination with hemophagocytic lymphohistiocytosis (HLH) (p<0.001), clinical stage more than III (p=0.014), IPI score above 3 (p=0.049), and bone marrow involvement (p=0.010) were the independent prognostic factors significantly associated with worse OS and PFS. Additionally, pegylated liposomal doxorubicin (PLD)-containing chemotherapy regimen could bring a higher overall response rate (ORR) and prolong the survival of patients with PTCL who underwent ASCT. ASCT may improve the long-term survival of patients with PTCL as consolidation therapy after achieving complete or partial remission of induction treatment, particularly for those with high risks. The chemotherapy regimen containing pegylated liposomal doxorubicin may induce deeper remission than traditional doxorubicin in PTCL. It is crucial to identify the specific groups most likely to benefit from upfront ASCT.

The impact of race and ethnicity on diffuse large B-cell lymphoma outcomes within the veterans health administration (VHA)

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort (p < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status. Outcomes analysis revealed similar treatment, response rates, median overall survival, and 1-, 3-, and 5-year survival across all subgroups. Hispanic patients had a 21% lower risk of death (HR = 0.79) than white patients, and Black patients had no significant difference in survival (HR = 0.98). This large retrospective study shows that when standard of care therapy is given within an equal access system, short-term treatment and survival outcomes are the same for all races.

A Real-World Single-Center Study of Adult Hodgkin's Lymphoma

To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, β2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma

To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. Patients were divided into low B-cell count group (B cell＜0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated β2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.